RESUMO
The mechanisms protecting from immunopathology during acute bacterial infections are incompletely known. We found that in response to apoptotic immune cells and live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti-atherogenic lipid exchange mediator, activated internalization mechanisms with characteristics of macropinocytosis and, assisted by Golgi fragmentation, initiated autophagic responses. This was supported by scavenger receptor-induced local increases in membrane cholesterol concentrations which generated lipid domains particularly in cell extensions and the Golgi. SR-BI was a key driver of beclin-1-dependent autophagy during acute bacterial infection of the liver and spleen. Autophagy regulated tissue infiltration of neutrophils, suppressed accumulation of Ly6C+ (inflammatory) macrophages, and prevented hepatocyte necrosis in the core of infectious foci. Perifocal levels of Ly6C+ macrophages and Ly6C- macrophages were unaffected, indicating predominant regulation of the focus core. SR-BI-triggered autophagy promoted co-elimination of apoptotic immune cells and dead bacteria but barely influenced bacterial sequestration and survival or inflammasome activation, thus exclusively counteracting damage inflicted by immune responses. Hence, SR-BI- and autophagy promote a surveillance pathway that partially responds to products of antimicrobial defenses and selectively prevents immunity-induced damage during acute infection. Our findings suggest that control of infection-associated immunopathology can be based on a unified defense operation.
Assuntos
Autofagia/imunologia , Macrófagos/imunologia , Microdomínios da Membrana/imunologia , Pinocitose/imunologia , Receptores Depuradores Classe B/imunologia , Animais , Autofagia/genética , Proteína Beclina-1/genética , Proteína Beclina-1/imunologia , Complexo de Golgi/genética , Complexo de Golgi/imunologia , Listeria monocytogenes/imunologia , Listeriose/genética , Listeriose/imunologia , Listeriose/patologia , Hepatopatias/genética , Hepatopatias/imunologia , Hepatopatias/patologia , Macrófagos/patologia , Microdomínios da Membrana/genética , Camundongos , Camundongos Knockout , Infiltração de Neutrófilos/genética , Infiltração de Neutrófilos/imunologia , Neutrófilos/imunologia , Neutrófilos/patologia , Pinocitose/genética , Receptores Depuradores Classe B/genética , Esplenopatias/genética , Esplenopatias/imunologia , Esplenopatias/patologiaRESUMO
Members of the genus Wolbachia are intracellular bacteria that are widespread in arthropods and establish diverse symbiotic associations with their hosts, ranging from mutualism to parasitism. Here we present the first detailed analyses of Wolbachia in butterflies from India with screening of 56 species. Twenty-nine species (52%) representing five families were positive for Wolbachia. This is the first report of Wolbachia infection in 27 of the 29 species; the other two were reported previously. This study also provides the first evidence of infection in the family Papilionidae. A striking diversity was observed among Wolbachia strains in butterfly hosts based on five multilocus sequence typing (MLST) genes, with 15 different sequence types (STs). Thirteen STs are new to the MLST database, whereas ST41 and ST125 were reported earlier. Some of the same host species from this study carried distinctly different Wolbachia strains, whereas the same or different butterfly hosts also harbored closely related Wolbachia strains. Butterfly-associated STs in the Indian sample originated by recombination and point mutation, further supporting the role of both processes in generating Wolbachia diversity. Recombination was detected only among the STs in this study and not in those from the MLST database. Most of the strains were remarkably similar in their wsp genotype, despite divergence in MLST. Only two wsp alleles were found among 25 individuals with complete hypervariable region (HVR) peptide profiles. Although both wsp and MLST show variability, MLST gives better separation between the strains. Completely different STs were characterized for the individuals sharing the same wsp alleles.
Assuntos
Borboletas/microbiologia , Variação Genética , Tipagem de Sequências Multilocus , Wolbachia/classificação , Wolbachia/genética , Animais , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , Genótipo , Índia , Dados de Sequência Molecular , Recombinação GenéticaRESUMO
Blood neutrophils provide the first line of defense against pathogens but have also been implicated in thrombotic processes. This dual function of neutrophils could reflect an evolutionarily conserved association between blood coagulation and antimicrobial defense, although the molecular determinants and in vivo significance of this association remain unclear. Here we show that major microbicidal effectors of neutrophils, the serine proteases neutrophil elastase and cathepsin G, together with externalized nucleosomes, promote coagulation and intravascular thrombus growth in vivo. The serine proteases and extracellular nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a process involving local proteolysis of the coagulation suppressor tissue factor pathway inhibitor. During systemic infection, activation of coagulation fosters compartmentalization of bacteria in liver microvessels and reduces bacterial invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived serine proteases and nucleosomes can contribute to large-vessel thrombosis, the main trigger of myocardial infarction and stroke. The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense.
Assuntos
Coagulação Sanguínea/genética , Imunidade Inata/genética , Neutrófilos/fisiologia , Serina Proteases/fisiologia , Animais , Coagulação Sanguínea/fisiologia , Fatores de Coagulação Sanguínea/metabolismo , Fatores de Coagulação Sanguínea/fisiologia , Catepsina G/genética , Catepsina G/metabolismo , Catepsina G/fisiologia , Fibrina/metabolismo , Imunidade Inata/fisiologia , Elastase de Leucócito/genética , Elastase de Leucócito/metabolismo , Elastase de Leucócito/fisiologia , Lipoproteínas/metabolismo , Camundongos , Camundongos Knockout , Modelos Biológicos , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Neutrófilos/metabolismo , Nucleossomos/metabolismo , Processamento de Proteína Pós-Traducional/genética , Processamento de Proteína Pós-Traducional/fisiologia , Serina Proteases/genética , Serina Proteases/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/metabolismoRESUMO
The intracellular bacteria, Wolbachia, are well known for inducing reproductive alterations in arthropod hosts, especially insects. The ancient origin and huge diversity, combined with the ecological, biological and behavioral plasticity of termites, make the latter exciting candidates for studying the interactions of Wolbachia. In the present study, we investigated the distribution of Wolbachia in populations of Odontotermes spp. and Coptotermes heimi termites occurring in 14 colonies (12 Odontotermes spp. and two C. heimi) from different locations in India. A striking diversity was observed among Wolbachia strains in closely related hosts based on five MLST genes (ftsZ, coxA, fbpA, hcpA and gatB) and the 16S rRNA gene. Wolbachia variants from two supergroups (B and F) were found in both the termite genera under study. This is the first report of Wolbachia infection in the Odontotermes genus. Although F Wolbachia supergroup infection is already reported in Coptotermes lacteus and Coptotermes acinaciformis, in this study, the two C. heimi species exhibited infection by two distinctly different Wolbachia supergroups (B and F).
